News : Inborn Errors of Metabolism (IEM)

Excerpt from STAR ONLINE

Screening them at birth
By LOH FOON FONG

The mystery has haunted many grieving parents: why do their normal, healthy babies suddenly become handicapped or mentally retarded? But such are the insidious effects of infants with Inborn Errors of Metabolism (IEM), inherited metabolic diseases that comprise a large class of genetic diseases.

“A baby may be well until suddenly at three years old, he or she dies of a heart attack,” said Dr Choy Yew Sing, geneticist-cum-metabolic-specialist at the Kuala Lumpur Hospital (KLH).
Cases detected in Malaysia are just the tip of the iceberg. Many have gone unnoticed because the symptoms are common: heart attack, stroke, poor feeding, fits, comatose, behavioural problems, hearing or visual problems, bleeding in the head, vomiting blood or autism, he said.

Dr Choy Yew Sing: ‘Deficiency in enzymes due to defective genes can affect any organ in the body.“Deficiency in enzymes due to defective genes can affect any organ in the body,” explained Dr Choy, who diagnoses at least four new cases weekly. “If untreated, they may cause mental retardation, physical handicap and even death.
“Many of the diseases resulting from IEM are treatable, if only they are detected early,” he said.
Hence, newborn screening, early diagnosis and appropriate management would save the child and prevent mental retardation and physical handicaps, he said.
He said, generally, treatment would be futile when a child reached age seven.
An affected individual inherits the defective gene from both parents who are carriers but are themselves normal.

Examples of the more common IEM are: G6PD deficiency, maple syrup urine disease, urea cycle defects, methylmalonic academia, mucopolysaccharidosis and mitochondrial disease.
The symptoms range from mild to severe. The condition usually affects babies although some symptoms are manifested only in adulthood, said Dr Choy.
He said if the symptoms indicate usual health problems, proper standard treatment would rectify them.

But with IEM, the problem will recur and worsen, even after treatment.
He said the problem cuts across all ethnic groups; marriage between relatives increases the risk.
He said the lack of expertise and IEM testing facilities has resulted in the lack of detection. There are only three geneticists in Malaysia who are trained to detect IEM, and only the Institute for Medical Research and Kuala Lumpur Hospital have the facilities and expertise to conduct the tests, said Choy.

The screening process for IEM includes special blood (serum amino acid) and urine (uric organic acid) tests of newborns by using the technology called tandem mass spectrometry.
Currently, there are more than 1,000 patients on record. Since one in 1,500 children is born with the condition, there may be more than 300,000 cases a year from the 500,000 babies born in Malaysia every year, said Dr Choy.

The Health Ministry had initiated the project to look into the feasibility of screening all newborn babies for genetic metabolic disorder. The two-year project is currently being carried out at government hospitals in Kuala Lumpur, Putrajaya, Selayang, Alor Star, Penang, Kota Baru, Kuching and Malacca, said Dr Choy.

“We want to see how prevalent IEM is in our population and how feasible the treatment process is so that we can plan for the health needs of the population,” he said.

“Screening babies at birth allows for early treatment and preventing complications,” he said. “It also reduces the extent of brain damage and organ failure.”

Depending on the type of IEM, patients can be treated with special diet, vitamin supplements, medications, enzyme replacements, liver transplants or bone marrow transplant, said Dr Choy.

For further information, contact Norliya 012-315 5421, Ivy 017-330 2632 or Chan 012-338 1706.

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Related Article

Banking on hope
By LOH FOON FONG

The CT scan results for the four-month-old boy looked suspicious. They showed bleeding in the head, caused either by a fall or abuse. Doctors queried Winnie Chan, the baby’s mother, if either had taken place. She denied it, but was deeply troubled by the questions.

She had brought Chang How Nam to the hospital because he had difficulty swallowing, could not grip with his hands or initiate movements.

It was not until Chang was seven that his condition was diagnosed. The cause: glutaric aciduria type I, a rare genetic disorder in which the body is unable to process the amino acid lysine, hydroxylysine and tryptophan properly. He suffered brain damage that resulted in mental retardation.

Some people with glutaric aciduria develop bleeding in the head (subdural haemorrhage) and the bleeding can be mistaken for acts of child abuse, said Dr Choy Yew Sing, chief investigator of the Health Ministry’s pilot project, Newborn Screening for Inborn Errors of Metabolism (IEM), which started on Sept 1.

“Bleeding could be mistaken for acts of child abuse,’’ he explained.

How Nam was misdiagnosed due to the general lack of expertise in Malaysia. As he grew, he could not sit, crawl or call his parents. Now, at 12 , he cannot stand, walk, speak or swallow food because the right diagnosis came too late.

Tan Yee Ping using the computer to communicate with his only brother. Beside him is his father, C.L. Tan.“I was told that if his condition had been known earlier, he would be able to talk and walk,” said 47-year-old Chan.

She had brought her son to many specialists and ended up in a neuro clinic. He was treated as a cerebral palsy case but his condition continued to worsen.

“I could not accept it. He was normal until he was four months old. I insisted that the doctor carry out an MRI scan for him because he was not getting better despite all the treatment,” she said.

The neurosurgeons then decided to refer her case to a geneticist. Special blood and urine tests were done. That was when his condition was finally diagnosed, in 2004.

“I was so relieved when we finally found out what was really wrong with him,” she said.

Tan Yee Ping, at 17, before he was diagnosed with Inborn Errors of Metabolism.How Nam now takes 10 different types of medication and vitamin supplements. His condition has affected his capacity to swallow, so an opening is created at the abdomen to feed him.

“I am glad that the Health Ministry is looking into the possibility of making IEM screening available to all newborns in future. Then cases such as mine could be prevented,” she said.
Tan Yee Ping was a normal, healthy baby until he started having fits at around four and a half months, recalled his 57-year-old retiree father C. L. Tan.

“He would have more than 20 fits a day and it was impossible for us to feed him. We saw a lot of doctors and they would give medication. But the medication did not stop the fits. It only reduced (the frequency),” said Tan.

“The doctors said he was epileptic and told me that when his immunity is stronger by the time he is 15, the fits might go away,” he said.

However, they did not. Yee Ping grew up thinner and smaller than most children his age. He could not sit or stand, and he salivated all the time. Every two or three hours, he would need to lie down because he would be tired.

“Yee Ping has run out of ‘battery,’ the teachers would say and let him rest,” recalled Tan.
His condition shifted between being as soft as jelly when he was not having a fit, and stiff when he had one, Tan said.

Two years ago, when Yee Ping was 18, Tan brought him to see a paediatrician in Universiti Kebangsaan Malaysia Hospital.

Coincidentally, Yee Ping had a fit at that time and the doctor saw his seizure. He said that it was not epilepsy but some kind of neurotransmitter disorder due to the lack of certain enzymes, said Tan.

“He referred me to a specialist at KLH,’’ he added. The specialist had just returned from overseas and had set up a special clinic called the metabolic clinic. I didn’t know what metabolic disorder was,” he said.

The geneticist saw his son, asked him to walk and told Tan that it could be a neuro-transmitter disorder. He took blood and urine samples and wanted to admit Yee Ping the following week to take some spinal fluid.

“One of my relatives told me that his child became abnormal as a result of spinal fluid being removed from him while others told me that it would be a high risk procedure. I was troubled. I had to make a decision and I decided to admit Yee Ping,” he said.

After the spinal fluid was removed, Yee Ping felt dizzy, vomited and could not sit up, the side effects from the procedure. He stayed in the hospital for five days before he was discharged.

Test results showed he suffered from tetrahydrobiopterin deficiency, a rare disorder that increases the blood levels of a substance called phenylalanine.

The specialist changed all the medication except for the one that treated seizures. The treatment helped him produce the enzyme that he lacked.

He suffered side effects for more than a month due to the change in medication but within six months, Yee Ping, who had never walked since he was born, began walking.

“He is literally a walking miracle,” said Tan, tears welling up in his eyes.

“He became physically stronger and more alert, unlike before, often in a daze due to fits and medication. No more floppy eyes, sleepiness or frequent fits. Now he is undergoing speech therapy,” he added.

From 20 fits a day to about six when Yee Ping was under medication, it is now down to once or twice a year.

When asked what he hopes for the future, Yee Ping, with his slurred speech, said he wants to be a policeman.

[tags : seic epilepsy seizures children pediatric neurology]